Targeted Therapy for Solid Tumors
Palo Alto (17 mi)Overseen byJames M Ford
Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.
What data supports the idea that Targeted Therapy for Solid Tumors is an effective treatment?The available research shows that the drug binimetinib, when used in combination with other treatments, has shown effectiveness in treating certain types of cancers. For example, in patients with advanced solid tumors with specific genetic changes (RAS/RAF alterations), binimetinib combined with another drug was studied for safety and effectiveness. Additionally, binimetinib has been approved for use with another drug to treat a type of skin cancer called melanoma, especially when certain mutations are present. Studies also explored its use in other cancers like colorectal cancer and lung cancer, showing potential benefits. This suggests that targeted therapy using binimetinib can be effective, particularly when tailored to specific genetic profiles of tumors.567810
Do I need to stop my current medications for this trial?The protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.
What safety data is available for targeted therapy using Binimetinib?Binimetinib has been evaluated in several studies for its safety profile. It was approved in 2018 for use in combination with encorafenib for metastatic melanomas, showing potent efficacy in cancers with BRAF and NRAS mutations. A phase Ib study investigated its safety in combination with buparlisib for advanced solid tumors with RAS/RAF alterations. Another phase II study demonstrated an acceptable safety profile for the combination of encorafenib and binimetinib in BRAFV600E-mutant metastatic non-small-cell lung cancer. Additionally, a phase 1 study determined the maximum tolerated dose and safety profile of binimetinib in patients with advanced solid tumors, including those with biliary cancer or KRAS- or BRAF-mutant colorectal cancer.578911
Is the drug combination of Binimetinib, Fulvestrant, Ipatasertib, Leucovorin, Nilotinib Hydrochloride Monohydrate, Olaparib, Palbociclib, Selumetinib Sulfate, and Sotorasib promising for treating solid tumors?Yes, the combination of these drugs is promising for treating solid tumors. Targeted therapies like these are designed to attack specific genetic or immunological changes in tumors, which can lead to better survival rates and improved treatment outcomes. These drugs are part of a new wave of treatments that have shown significant potential in clinical trials for various types of cancer.12346
Eligibility Criteria
This trial is for adults with advanced solid tumors that have spread and are not responding to standard treatments or lack treatment options proven to extend life. Participants need available tumor tissue samples, must be in fair health (ECOG 0-2), and willing to undergo genetic testing of their tumors. It's not suitable for those who've had a good response to recent therapies.Inclusion Criteria
My condition worsened after at least one standard treatment.
I am over 18 and can provide a sample of my tumor for research if I join the trial.
I haven't had significant tumor shrinkage after my last treatment.
I am under 18 and can provide a sample of my tumor for research if I join the trial.
My cancer tissue samples are available for testing.
My condition has no proven treatment to extend life.
I am 18 or older and can have a low-risk biopsy for research if I join a ComboMATCH trial.
Treatment Details
The ComboMATCH trial tests targeted therapies based on genetic mutations in patients' tumors. Various drugs like Oxaliplatin, Ipatasertib, and Olaparib are matched with specific genetic changes identified through testing. The study aims to control the tumor growth by personalizing treatment plans.
20Treatment groups
Experimental Treatment
Active Control
Group I: EAY191-S3 (activating AKT mutation)Experimental Treatment6 Interventions
Patients receive paclitaxel IV and ipatasertib PO on study. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and follow-up.
Group II: EAY191-N5 Arm II (neratinib maleate,palbociclib)Experimental Treatment8 Interventions
Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
Group III: EAY191-N4 Arm I (RAS pathway mutations)Experimental Treatment9 Interventions
Patients receive selumetinib PO and olaparib PO on study. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
Group IV: EAY191-N2 Cohort II (NF1 mutations)Experimental Treatment9 Interventions
Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.
Group V: EAY191-N2 Cohort I (Arm II) (NF1 mutations)Experimental Treatment8 Interventions
Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.
Group VI: EAY191-N2 Cohort I (Arm I) (NF1 mutations)Experimental Treatment9 Interventions
Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.
Group VII: EAY191-E5 Cohort II (sotorasib)Experimental Treatment6 Interventions
Patients receive combination therapy as in EAY191-E5 Arm A.
Group VIII: EAY191-E5 Cohort I Arm A (sotorasib, panitumumab)Experimental Treatment6 Interventions
Patients receive sotorasib PO QD on days 1-28 and panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.
Group IX: EAY191-E4 (taxane therapy)Experimental Treatment6 Interventions
Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression.
Group X: EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations)Experimental Treatment11 Interventions
Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated
Group XI: EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations)Experimental Treatment11 Interventions
Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or a FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.
Group XII: EAY191-A3 Monotherapy Cohort 1 (binimetinib)Experimental Treatment6 Interventions
Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Group XIII: EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)Experimental Treatment6 Interventions
Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Group XIV: EAY191-A2 (Cohort 3, Arm D)Experimental Treatment7 Interventions
Cohort 3, Arm D: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
Group XV: EAY191-A2 (Cohort 2, Arm C)Experimental Treatment7 Interventions
Cohort 2, Arm C: Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
Group XVI: EAY191-A2 (Cohort 2, Arm B)Experimental Treatment8 Interventions
Cohort 2, Arm B: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
Group XVII: EAY191-A2 (Cohort 1, Arm A)Experimental Treatment8 Interventions
Cohort 1, Arm A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
Group XVIII: EAY191-N5 Arm I (neratinib maleate)Active Control7 Interventions
Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
Group XIX: EAY191-E5 Cohort I Arm B (sotorasib)Active Control5 Interventions
Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.
Group XX: EAY191-N4 Arm II (RAS pathway mutations)Active Control8 Interventions
Patients receive selumetinib PO on study. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Mektovi for:
- Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
🇪🇺 Approved in European Union as Mektovi for:
- Unresectable or metastatic melanoma with a BRAF V600 mutation
🇨🇦 Approved in Canada as Mektovi for:
- Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
🇯🇵 Approved in Japan as Mektovi for:
- Unresectable or metastatic melanoma with a BRAF V600 mutation
Find a clinic near you
Research locations nearbySelect from list below to view details:
Loyola University Medical CenterMaywood, IL
University of Michigan Comprehensive Cancer CenterAnn Arbor, MI
Dana-Farber Cancer InstituteBoston, MA
Dublin Methodist HospitalDublin, OH
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours. [2021]Sunitinib is a multitargeted, oral tyrosine kinase inhibitor with antitumour and antiangiogenic activity. We investigated the safety and pharmacokinetics of sunitinib in combination with irinotecan in patients with advanced, refractory solid tumours.
Response and safety of sunitinib in a heavily pre-treated metastatic non-small cell lung carcinoma patient. [2018]The activity of sunitinib, a multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activities, has been explored in several solid malignancies such as breast, lung, prostate and pancreatic cancer. Currently it is approved for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Non-small cell lung cancer usually presents at an advanced or metastatic stage at diagnosis. Treatment options are limited for this disease, therefore symptom palliation and patient's quality of life are primary objectives of therapy.
Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). [2022]The prognosis for patients with relapsed/progressive non-small cell lung cancer (NSCLC) remains poor. For first-line therapy, a number of platinum-based regimens are standard; second-line therapies include single-agent docetaxel, pemetrexed, and erlotinib. Treatment options for patients whose tumors have failed to respond to two or more conventional chemotherapy regimens are limited, with erlotinib, which targets the epidermal growth factor receptor, and crizotinib, which targets EML4/ALK, the only agents currently approved in the United States as third-line therapy for patients with advanced/metastatic NSCLC. Among the targeted agents that have undergone evaluation for third-line therapy and beyond are afatinib, apatinib, axitinib, AUY922, pazopanib, sorafenib, sunitinib, and vandetanib. Agents that affect multiple pathways have the potential to provide significant clinical benefits. Identifying molecular characteristics that make tumors more likely to respond to a targeted therapy is crucial. This article reviews the hypotheses and data that provide the rationale for the development of targeted agents for third- and fourth-line treatment of patients with relapsed/refractory NSCLC.
[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin-bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents.
A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. [2022]Binimetinib (MEK162; ARRY-438162) is a potent and selective oral MEK 1/2 inhibitor. This phase 1 study determined the maximum tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic profiles, and preliminary anti-tumour activity of binimetinib in patients with advanced solid tumours, with expansion cohorts of patients with biliary cancer or KRAS- or BRAF-mutant colorectal cancer.
A phase I clinical trial of binimetinib in combination with FOLFOX in patients with advanced metastatic colorectal cancer who failed prior standard therapy. [2022]This was a first in-human, open-label, dose-escalation phase I study conducted to evaluate the maximum tolerated dose (MTD), safety, and efficacy of the combination of oral binimetinib and FOLFOX.
Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. [2023]This multicenter, open-label, phase Ib study investigated the safety and efficacy of binimetinib (MEK inhibitor) in combination with buparlisib (phosphatidylinositol 3-kinase [PI3K] inhibitor) in patients with advanced solid tumors with RAS/RAF alterations.
The discovery and development of binimetinib for the treatment of melanoma. [2021]Label="INTRODUCTION">Binimetinib is an uncompetitive, small-molecule inhibitor of selective mitogen-activated protein kinase (MEK1/2) and was recently approved in 2018 in combination with encorafenib for the treatment of metastatic melanomas. Preclinical and clinical trial data on the drug demonstrate its potent efficacy in cancers, especially melanomas with BRAF and NRAS mutations.
Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023]To explore the safety of osimertinib plus ramucirumab in patients with EGFR-mutated lung adenocarcinoma.
A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer. [2021]MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690).
Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. [2023]Label="PURPOSE">The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAFV600E/K-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC).